Method and compositions for inhibiting or preventing adverse effects of oral antibiotics

The method of any one of the above claims, wherein the protection of the subject's microbiome comprises maintenance of a normal intestinal microbiota.

The method of any one of the above claims, wherein the method treats and/or prevents the overgrowth of one or more pathogenic microorganisms in the GI tract of a subject.

The method of any one of the above claims, wherein the method treats or prevents a nosocomial infection and/or a secondary emergent infection.

The method of any one of the above claims, wherein an initial and/or adjunctive therapy is administered to the subject.

The method of any one of the above claims, wherein the beta-lactamase does not substantially interfere with plasma levels of a systemically absorbed orally administered antibiotic.

The method of any one of the above claims, wherein the beta-lactamase deactivates residual oral antibiotic residue excreted into the GI tract, wherein the residual oral antibiotic is not absorbed from the GI tract after an oral dose or is returned in active form to the intestinal tract from the systemic circulation.

The method of any one of the above claims, wherein the beta-lactamase is formulated for GI tract delivery.

The method of any one of the above claims, wherein the beta-lactamase is one or more of class A, B, C, or D beta-lactamase.

The method of any one of the above claims, wherein the beta-lactamase has a KM of less than about 500 μM, or about 100 μM, or about 10 μM, or about 1 μM, or about 0.1 μM, or about 0.01 μM, or about 1 ηM for one or more oral antibiotics.

The method of any one of the above claims, wherein the beta-lactamase has a Vmax of greater than about 100 s−1, or about 1000 s−1, or about 10000 s−1, or about 100000 s−1, or about 1000000 s−1 for one or more oral antibiotics.

The method of any one of the above claims, wherein the beta-lactamase has a catalytic efficiency that is greater than about 106 M−1 s−1 for one or more oral antibiotics.

The method of any one of the above claims, wherein the subject has previously suffered from a microbiome-mediated disorder.

The method of any one of the above claims, wherein the subject present symptoms of recurrence of a microbiome-mediated disorder.

The method of any one of the above claims, wherein the orally administered antibiotic is selected from one or more of penicillins, cephalosporins, monobactams, and carbapenems.

The method of any one of the above claims, further comprising administering a beta-lactamase inhibitor that releases in the GI tract proximal to the beta-lactamase.

The method of any one of the above claims, wherein the beta-lactamase is formulated for microorganism-based release.

A method of protecting a subject's gastrointestinal microbiome, comprising administering an effective amount of a pharmaceutical composition comprising P3A beta-lactamase to a subject who is undergoing treatment or has recently undergone treatment with orally-administered amoxicillin, wherein the P3A is delivered to the GI tract and deactivates the oral antibiotic in the GI tract.

A method for preventing antibiotic-induced diarrhea and/or C. difficile infection (CDI), comprising administering an effective amount of a pharmaceutical composition comprising P3A beta-lactamase to a subject at risk for antibiotic-induced diarrhea and/or C. difficile infection (CDI), wherein:

• the P3A is delivered to the subject's GI tract and deactivates the oral antibiotic in the GI tract and
• the subject is undergoing treatment or has recently undergone treatment with orally-administered amoxicillin.

A method of preventing an antibiotic-associated adverse effect in a subject in need thereof, comprising administering an effective amount of any of the beta-lactamase formulation disclosed herein, and

• wherein the antibiotic is an oral antibiotic, the oral antibiotic being a substrate for the beta-lactamase;
• and
• wherein the subject is undergoing treatment with the oral antibiotic.